Peter Kloehn
Peter Kloehn
Cellular mechanisms
of prion propagation

Peter obtained a diploma in Biochemistry in 1992 at the University of Freiburg, Germany and undertook his PhD in cancer research at the Julius-Maximilians University Wurzburg. His interest in liver cancer led him to pursue his post-doctoral work at the Karlsruhe Institute of Technology in Germany and at the University of Medical Research in Padova, Italy from 1997 to 2000.

In 2001, Peter joined Professor John Collinge’s Department at the MRC Prion Unit to generate cell models of prion disease in a post-doctoral research post with Professor Charles Weissmann. He is currently a Programme Leader with the MRC Prion Unit and Senior Lecturer at University College London. Peter’s main pursuit is to develop cell models to study molecular disease pathways in Prion and Alzheimer’s disease. He has a strong track record in cell biology and wide-ranging expertise in genetic engineering and molecular imaging.

Prions are infectious agents that cause the lethal brain disease CJD in humans and they infect a range of different cells in the body. Most studies of prions have required use of laboratory animals but more recently it has been possible to produce types of cells that can be grown indefinitely in the laboratory and used to propagate prions. However, it turns out to be very difficult to find cells that propagate prions efficiently in the laboratory and the ones that do, will typically only propagate just one type, or strain, of prions. By studying different lines of cells that are highly susceptible to defined prion strains, we aim to work out the crucial factors that make them susceptible to specific strains. We also want to understand how prions pass from cell to cell. Such knowledge will help us develop better cell systems to study prions, reduce the need to use animals, and provide fundamental insights into the mechanisms of prion propagation which will ultimately help us develop better tests and treatments for these diseases in the future.

The aims of this programme are (1) to find cellular factors required for the propagation of prions and (2) to better understand reasons for the selective vulnerability of the brain to different prion strains.

(1) Cell lines have been recognised as very useful tools for prion detection and assay, since the cell-based amplification of prions increases sensitivity levels by about 1,000 to 10,000 times when compared to conventional protein assays. To date, the number of cell lines in which prions can be propagated long term is very limited. In addition, the majority of prion-susceptible cell lines are permissive only to one or two mouse-adapted prion strains, but not to ovine, bovine or human prions. Understanding the cellular factors mediating prion propagation is of major importance to the field. We recently identified a set of genes that are linked to prion propagation and we now examine how these genes affect prion disease.

(2) Certain prion strains affect specific regions in the brain, but the reasons for the selective vulnerability of the brain to different prion strains is not understood. Strains are not exclusive to prion diseases, but have also been described for other dementia diseases, like Alzheimer’s disease.

Insights into the molecular factors that determine selective vulnerability of the brain to distinct strains could therefore help to better understand the strain phenomenon in dementia diseases. To find such factors we select cells that exclusively propagate one prion strain, but not others and then examine the reasons for selective susceptibility. Once we identify critical factors in cells, we can examine how they affect brain damage and whether this tells us something about selective vulnerability.